We propose to examine how stressful situations affect biochemical processes that in turn have important effects on behavior. The biochemical processes we will study involve brain monoamines because monoamines are implicated in abnormal behavior, particularly depression and schizophrenia. Previous research in our laboratory and others has found that animals receiving inescapable shock show changes in brain norepinephrine as well as deficits in active motor behavior, whereas animals that receive the same shocks in the course of performing an effective coping response do not show these brain norepinephrine changes and are not behaviorally impaired. The objective of this research is to specify more precisely how inescapable shock affects monoamines so as to depress active avoidance-escape responding and motor activity. The first part of the research examines in detail which of the monoamines (norepinephrine, dopamine, and serotonin) and, most important, which interactions between amine systems, play an important role in mediating motor activity and active avoidance-escape behavior in our testing situations. These studies evaluate the role of aminergic systems by measuring behavior after making lesions (by neurotoxins) or blocking monoamine systems by drugs. In the second part of the research, we study how inescapable shock affects monoamines, studying how it alters monoamine level, uptake, and receptor sensitivity. Shock-induced changes in levels of the three monoamines are followed over time after the stress session and these changes are correlated with changes in avoidance-escape behavior. We then study changes in uptake, which are likely to have significant effects on behavior since uptake influences the amount of receptor stimulation. Uptake of dopamine and serotonin particularly are examined. Accumulation of 3H amines is studied in vitro and in vivo. Finally, possible effects of inescapable shock on receptor sensitivity are explored. We use as indicators of receptor sensitivity changes in (a) body temperature, (b) motor-related behavior in response to monoamine agonists, and (c) the cyclic AMP response to monoamines in vitro.